A Study on Oral and Intranasal Forms of Oxycodone in Healthy Volunteers Using Pharmacokinetic Modeling

Physiologically Based Pharmacokinetic Modelling of Oral and Intranasal Formulations of Oxycodone in Healthy Volunteers

This is a single-dose, 2-period, 2-sequence, fasting, open label, crossover randomized design, comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of intranasal and oral oxycodone solutions. The aim will be to characterize the PK and PD of two formulations of oxycodone (intranasal and oral) in healthy subjects, which will be used to verify/validate nasal-CNS-PBPK (Physiologically Based Pharmacokinetic) model predictions following intranasal dosing. A total of 8 healthy male/female subjects will be randomly assigned to one of two sequences in the crossover study. All subjects will receive the same dosage of oxycodone intranasal or oral and the sequence will be determined following randomization.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Physiologically Based Pharmacokinetic
• Intervention / Treatment: Drug: oxycodone; Drug: Oxycodone IN

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Hospital del Mar Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male or female volunteers according to physical examination, vital signs (blood pressure, heart rate and body temperature), ECG and safety laboratory parameters and results should be within normal ranges or considered as non-clinically relevant by the investigator.
• Age ≥ 18 and ≤ 55 years.
• Body weight up to 90 kg
• Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2.
• Able/willing to be compliant with the study restrictions
• Able to read Spanish and adhere to study requirements.
• Signed informed consent prior to any study-mandated procedure.
• Prior therapeutic or recreational experience with opioids (i.e., tramadol, oxycodone, or buprenorphine)

Exclusion Criteria:

• Life-time (current and/or history of) substance use disorders (SUD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
• Use of any illegal drug within 30 days of screening and throughout participation in the study
• History of smoking or use of nicotine containing products within 3 months of screening and throughout participation in the study
• No acute, chronic, or allergic rhinitis
• Ongoing gastrointestinal diseases or history of gastrointestinal surgery affecting absorption.
• History of severe bronchial asthma or chronic obstructive pulmonary disease,
• Any anatomical abnormality or pathological condition of the nasal cavity based on medical history.
• History of hypothyroidism.
• Subjects with a clinically relevant disease or condition that in the judgment of the investigator might interfere with the safety or subject's ability to comply with study procedures or requirements and/or bias the interpretation of the study results and/or jeopardize the subject's safety.
• Current mental diseases that require prescription drugs.
• Any ophthalmologic condition that could interfere with pupillometry
• Being under any administrative or legal supervision.
• Pregnancy and breastfeeding
• Positive blood or urine test for drugs of abuse or alcohol breath test prior to study drug administration.
• Current and/or history of anxiety or depression not completely recovered within 12 months prior to study drug administration, as assessed by the Dual Diagnosis Screening Interview (DDSI).
• CYP2D6 poor or ultrarapid metabolizers.
• Any clinically relevant findings in physical examination, vital signs, 12-lead ECG and safety laboratory parameters.
• Positive hepatitis or HIV tests (Ag VHB, IgG VHC, Ac VIH).
• Known hypersensitivity to any drug or drug excipients.
• Use of drugs known to induce or inhibit hepatic drug metabolism (check drugs in Appendix 6) within one month prior to study administration or during the study and use of citrus juice during the study.
• Use of sedative medicines such as benzodiazepines or related drugs in the last 3 months.
• Any prescription or over-the-counter (OTC) product, not including oral contraceptives but including analgesics (paracetamol), aspirin, herbal, homeopathic, vitamins, minerals and nutritional supplements within one week prior to study drug administration.
• Intake of foods or beverages containing xanthine (more than 5 cups of coffee, tea or 5 bottles/cans cola drinks) per day.
• Donation of blood or plasma within two months prior to study drug administration
• Transfusion of blood or plasma for medical/surgical reasons in the past 120 days.
• Current or history of inadequate venous access and/or experience of difficulty donating blood.
• Subject included in a clinical trial within 3 months prior to study drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral oxycodone	Drug: oxycodone; oral solution 0.1 mg/kg
Experimental: intranasal oxycodone	Drug: Oxycodone IN; 0.1 mg/kg intravenously oxycodone solution administered intranasally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(0-24h)	Area under the curve from 0 time to the last measurable concentration (of intranasal and oral oxycodone), calculated from individual plasma PK concentrations.	up to 24 hours
Tmax	Time of maximum observed concentration (of intranasal and oral oxycodone), calculated from individual plasma PK concentrations.	Blood samples were taken pre-dose and up to 24 hours after start of each Dose
Cmax	The mean maximum observed concentration (of intranasal and oral oxycodone), calculated from individual plasma PK concentrations	Blood samples were taken pre-dose and up to 24 hours after start of each Dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Effects (AE)	AE was performed including number and percentage.	Up to 24 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pupil Diameter	To assess the effects of oxycodone on pupil size; only results at 24 hours will be reported.	up to 24 hours

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Collaborators: Food and Drug Administration (FDA); University of Manchester
• Investigators: Principal Investigator: Rafael De la Torre, PhD, Hospital del Mar Research Institute Barcelona

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2025
• Primary Completion (Actual): October 7, 2025
• Study Completion (Actual): October 7, 2025

Study Registration Dates

• First Submitted: May 9, 2025
• First Submitted That Met QC Criteria: October 30, 2025
• First Posted (Actual): October 31, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Codeine; Oxycodone
• Other Study ID Numbers: 2024-515461-34-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No